Sapanisertib + Bevacizumab for Glioblastoma

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anti-epileptics, Herbal supplements

Disqualifiers: Concurrent malignancy, CNS metastases, Cardiac arrhythmia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 2

Duration: 28 days per cycle, up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and assess the side effects of a new treatment combination for glioblastoma, a type of brain tumor, or other solid tumors unresponsive to standard treatments. The treatment includes a drug called MLN0128 (sapanisertib), which may inhibit tumor growth by blocking certain enzymes, and bevacizumab, which may prevent tumors from growing by stopping new blood vessel formation. Individuals with glioblastoma or certain advanced solid tumors that have not responded to other treatments might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before joining. You must stop using herbal supplements, non-traditional medications, and certain anti-coagulants before registration. If you're on enzyme-inducing anti-epileptic drugs, you need to stop them at least 10 days before starting the trial. Consult with the trial team about any other medications you are taking.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that Sapanisertib, a drug that blocks certain cell growth signals, is generally safe and well-tolerated by patients. However, specific safety information for using Sapanisertib with Bevacizumab is not yet available.

Other studies have shown Bevacizumab to be safe when combined with different treatments. About 5% of patients reported serious side effects, such as blood clots. Overall, both treatments have been studied and found to be generally safe, but their combined use is still under investigation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Sapanisertib (MLN0128) and Bevacizumab for glioblastoma because it offers a new way to tackle this aggressive brain cancer. Unlike standard treatments, which often target only one pathway, Sapanisertib is a TORC1/2 inhibitor that blocks critical signals cancer cells use to grow and survive. When combined with Bevacizumab, which inhibits blood vessel growth to the tumor, this duo could potentially halt tumor progression more effectively than current therapies. This dual approach might provide a more comprehensive attack on the cancer and could lead to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for glioblastoma?

In this trial, participants will receive a combination of sapanisertib and bevacizumab. Research has shown that sapanisertib, tested in lab models of human glioblastoma, may help stop tumor growth by blocking the mTOR pathway. This pathway is crucial for cell growth and survival, so blocking it could help control the tumor. Bevacizumab, a monoclonal antibody, has effectively treated recurrent glioblastoma by slowing tumor growth and preventing the formation of new blood vessels that tumors need. Studies indicate that about half of the patients taking bevacizumab with chemotherapy experienced more than four months without tumor progression. Together, these treatments aim to attack tumor growth in different ways, offering promise for patients with glioblastoma. ^{6 7 8 9 10}

Who Is on the Research Team?

Lakshmi Nayak

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with recurrent glioblastoma or advanced solid tumors that haven't responded to standard treatments. Participants must be able to swallow capsules, have no other concurrent cancers (except certain skin cancers), and use contraception if of child-bearing potential. They should not be on corticosteroids, pregnant, nursing, or have significant allergies to the drugs being tested.

Inclusion Criteria

Your blood and body chemistry need to be within certain limits.

I have a confirmed diagnosis of recurrent glioblastoma or an advanced cancer treatable with bevacizumab.

I have no other cancers except possibly treated skin cancer.

Exclusion Criteria

I have a stomach or intestine problem that affects how I absorb pills.

I haven't used specific growth factors recently.

I do not have uncontrolled high blood pressure, asthma, or diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive TORC1/2 inhibitor MLN0128 orally once daily and bevacizumab intravenously on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle, up to 2 years

2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up for 30 days and then annually thereafter.

30 days initially, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• MLN0128

Trial Overview The trial is testing a combination of TORC1/2 inhibitor MLN0128 and monoclonal antibody Bevacizumab in patients with specific types of brain and solid tumors. It aims to find the safest dose while assessing how these drugs might block tumor growth by inhibiting enzymes needed for cell growth and blood vessel formation.

How Is the Trial Designed?

Group I: Treatment (TORC1/2 inhibitor INK128, bevacizumab) Experimental Treatment 4 Interventions

Patients receive TORC1/2 inhibitor INK128 PO QD on days 1-28 and bevacizumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase II clinical trial involving 158 patients with newly diagnosed glioblastoma, cediranib combined with radiation and temozolomide significantly improved 6-month progression-free survival (PFS) to 46.6% compared to 24.5% for the placebo group (P = 0.005).

Although cediranib showed efficacy in prolonging PFS, it was associated with a higher incidence of grade ≥3 adverse events compared to placebo (P = 0.02), and there was no significant difference in overall survival between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NRG/RTOG 0837: Randomized, phase II, double-blind, placebo-controlled trial of chemoradiation with or without cediranib in newly diagnosed glioblastoma. Batchelor, TT., Won, M., Chakravarti, A., et al.[2023]

Bevacizumab (Avastin) received accelerated FDA approval for treating glioblastoma multiforme (GBM) based on its ability to produce partial responses in 25.9% of patients in one trial and 19.6% in another, with median response durations of approximately 4.2 and 3.9 months, respectively.

While bevacizumab shows efficacy in GBM treatment, it is associated with significant adverse events, including serious risks like CNS hemorrhage and thromboembolic events, highlighting the need for careful patient monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. Cohen, MH., Shen, YL., Keegan, P., et al.[2022]

In a retrospective analysis of 123 patients with recurrent glioblastoma, those treated with bevacizumab showed significant improvements in both progression-free survival (PFS) and overall survival (OS) compared to a control group.

Older patients (55 years and above) and those with poorer performance status benefited the most from bevacizumab treatment, suggesting that age-related biological differences in glioblastoma may influence treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab and chemotherapy for recurrent glioblastoma: a single-institution experience. Nghiemphu, PL., Liu, W., Lee, Y., et al.[2022]

Bevacizumab, a monoclonal antibody that targets VEGF, has shown promising results in treating recurrent glioblastoma multiforme (GBM), with notable response rates and progression-free survival at 6 months in various studies.

While early trials indicate that some patients may survive beyond 1 or 2 years on bevacizumab, definitive Phase III trial data are still needed to confirm its efficacy, and it is currently being tested in combination with other treatments for newly diagnosed GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in glioblastoma multiforme. Specenier, P.[2015]

Bevacizumab, used to treat glioblastoma and other tumors, has a unique toxicity profile that can lead to serious side effects like gastrointestinal perforation and intracranial hemorrhages, particularly in glioblastoma patients.

The study systematically reviewed these adverse events, identifying risk factors and suggesting preventive and therapeutic measures to reduce treatment-related complications, emphasizing the need for careful monitoring in patients receiving this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical management of bevacizumab-related toxicities in glioblastoma. Brandes, AA., Bartolotti, M., Tosoni, A., et al.[2022]

Bevacizumab, a monoclonal antibody targeting VEGF, shows a meaningful increase in progression-free survival for newly diagnosed glioblastoma patients, but it does not improve overall survival, highlighting the need for further research.

In recurrent glioblastoma patients, while bevacizumab has shown improved radiographic response and progression-free survival in uncontrolled trials, its effect on overall survival is still being evaluated in an ongoing randomized phase III trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The future of antiangiogenic treatment in glioblastoma. Chinot, OL., Reardon, DA.[2015]

A study of 310 glioblastoma patients from 2010 to 2014 found that the use of bevacizumab did not improve overall survival compared to patients treated before its approval, with median survival remaining similar at 13.5 months for IDH wild-type tumors.

However, patients receiving bevacizumab experienced a significant reduction in corticosteroid use during second-line treatment, suggesting a potential clinical benefit in managing treatment side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab may improve quality of life, but not overall survival in glioblastoma: an epidemiological study. Gramatzki, D., Roth, P., Rushing, EJ., et al.[2020]

Bevacizumab, a monoclonal antibody targeting VEGF, has shown improved patient outcomes in recurrent glioblastoma (GBM) when used in combination with chemotherapy, leading to its accelerated approval by the FDA based on positive results from phase 2 studies.

The treatment is associated with manageable toxicity, as severe adverse events occur in only a small percentage of patients, making it a safer option for those with recurrent GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab for the treatment of recurrent glioblastoma. Chamberlain, MC.[2023]

Citations

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Efficacy and safety of bevacizumab for the treatment of ... In addition, 57% of the patients (95% CI, 39–74%) demonstrated at least a partial response (PR), and the 4-year survival rate was demonstrated to be 11% in this ...

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Use of Bevacizumab in recurrent glioblastoma - BMC Cancer A phase II trial found that BEV plus ONA improved OS in patients with rGBM having unmethylated MGMT (mOS, ONA + BEV vs. PLA + BEV, 10.9 vs. 7.5 ...

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Avastin: How It's Used for Treating Glioblastoma In studies, about half the people receiving Avastin and chemotherapy for recurrent glioblastoma went 4.2 months without their tumor progressing.

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Avastin® (bevacizumab) Clinical Trials | rGBM Treatment Recurrent Glioblastoma: Avastin Efficacy Data. Recurrent glioblastoma (rGBM) Avastin is indicated for the treatment of recurrent glioblastoma in adults.

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Clinical Outcomes in Recurrent Glioblastoma with ... A previous review (995 patients) estimated a progression free survival (PFS) on BEV of 4.2 months (SD±2.1) with an overall survival (OS) after progression on ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.2057

Efficacy and safety of bevacizumab in combination with ... Results: Bevacizumab significantly improved PFS by a mean difference of 2.39 months (95% CI: 1.34 to 3.44; P = 0.0005), but no significant ...

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Benefits and Risks of Treatment for recurrent gliobastoma ... Serious to life threatening blood clots in the veins of the body were seen in 5% of patients receiving Avastin with chemotherapy compared to 2% of patients ...

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Study Details | NCT05271240 | Repeated Superselective ... The investigators have completed a Phase I clinical trial that has shown that Superselective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab (BV) is safe ...